One in four women has had a migraine. And, it turns out, the debilitating headaches affect three times more women than men.

But why?

Decades ago, these headaches were attributed to women's inability to cope with stress, a sort of hysteria. Now experts are starting to figure out the factors that really make a difference.

Today scientists know a migraine is all in your head — but not in that old-fashioned sense. Migraines are biologically based, and they play themselves out as a wave of electrical activity traveling across the brain.

Dr. Andrew Charles directs the Headache Research and Treatment Program in the UCLA Department of Neurology. He describes what occurs during a migraine as a "spectacular neuro-physiological event" that involves bursts of electrical activity that start in the vision center of the brain. That, Charles says, is why the headaches include a "visual aura, those jagged lines or sparkling lights, that commonly occur in 20 to 30 percent of migraine patients."

The brain activity then travels like a wave across the landscape of the brain, moving into areas that control sensation. Patients feel numbness or tingling, like pins and needles. Then the wave hits the area that controls language, and, when that happens, Charles says, "it can cause dramatic difficulty finding words or garbling of speech."

Charles says the pounding pain of a migraine is believed to be generated from deep within the brain. Some scientists think the wave of activity triggers the pain. Others, including Charles, think pain occurs simultaneously with the electrical wave as it traverses the brain.

What triggers a migraine is nearly as complicated as the migraine itself. There are environmental changes like sounds, light, smells and movement. There are genes; migraine risk is hereditary.

But there is one major trigger, and this is why women have so many more migraines than men.

Neurologist Jan Lewis Brandes, founder of the Nashville Neuroscience Group, says migraines can be triggered by hormonal fluctuation. Migraines are slightly more common in boys than girls until girls begin menstruation. And once girls begin to menstruate, and hormones begin to fluctuate up and down, the number of their migraines increases dramatically.

The main culprit is estrogen, although researchers think other hormones may also be involved. But the uncertainty contributes to the difficulty of migraine treatment.

There are drugs to reduce the pain and length of a migraine. Others cut down on the frequency of attacks. But there isn't a cure. As many as half of all patients say treatment isn't effective for them. And nearly all say they'd happily try a new treatment if it became available.

That's exactly what UCLA's Charles is trying to come up with in a lab that's stuffed with microscopes, cameras, lasers, computers and a few mice. Charles points to one mouse, under anesthesia, lying on its stomach under a scanner that tracks changes in brain activity after stimulation with a caffeine-like substance. Caffeine can trigger migraines in humans.

Finding effective treatment to reduce the number of attacks is critically important, says Charles, because "migraines beget migraines." The more of them you have, the more vulnerable you become to having another.

And that lends urgency to finding a way to reduce how often the headaches strike. "We've begun to see from researchers that the frequency of migraine attack is linked to permanent changes in the brain, and I think that changes the playing field for patients and those of us who take care" of them, Brandes says. "We really need to think carefully about how to control the frequency of attacks and really need to do it earlier rather than later."

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Transcript

LYNN NEARY, HOST:

This is MORNING EDITION from NPR News. I'm Lynn Neary.

STEVE INSKEEP, HOST:

And I'm Steve Inskeep. Good morning.

Today in Your Health, a new study sheds light on a disturbing trend among young people. First, though, we'll get a better understanding of migraines.

NEARY: These debilitating headaches affect far more women than men. Decades ago, such headaches were attributed to women's inability to cope with stress - a sort of hysteria.

INSKEEP: Today, scientists know its all in your head. But not in that old fashioned sense. Migraines are biologically based, waves of electrical activity travelling across the brain.

NPR's Pattti Neighmond has more.

PATTI NEIGHMOND, BYLINE: For Barbara Ige, 47 years old, an administrator at Santa Monica College in California, the migraines started when she was a child.

BARBARA IGE: I was always considered kind of broken. I was the weak kid.

NEIGHMOND: Sounds, smells, certain movements could make her sick.

IGE: Anytime there was a smog alert, anytime that somebody came in the house wearing strong perfume or smoking. I couldn't ride in the backseat of a car, because if I did I'd start to throw up and then I'd get these incredible migraines.

NEIGHMOND: Family and friends viewed her, she says, as melodramatic, maybe even making it all up. In fact, nothing could be further from the truth says Dr. Andrew Charles, a neurologist at UCLA School of Medicine.

DR. ANDREW CHARLES: This is a PET scan of a patient having a migraine. So this was a patient who was in the scanner for other studies, but serendipitously had a migraine attack while in the scanner.

CHARLES: You can see this spectacular wave of activity that spreads across the surface of the brain.

NEIGHMOND: Often beginning in the area of the brain that's involved in processing vision.

CHARLES: Which is why patients most commonly have visual aura, the jagged lines or sparkling lights that commonly occur in migraine patients. They occur in about 20 or 30 percent of migraine patients.

NEIGHMOND: The wave then travels to other regions of the brain, sensation centers. Patients may feel tingling or numbness. The wave can even reach into the brain's language center.

CHARLES: And when that occurs it can cause really quite dramatic difficulty finding words or garbling of speech.

NEIGHMOND: Thinking can get confused. And then there's the pain. Dr. Charles' patient Barbara Ige.

IGE: For me, it starts as a dull pain, and then I can feel the side of my face going numb. The pressure starts all across my forehead, and then I can't move. I usually put a heating pad over - I actually have to wear a heating pad over my head. I wrap myself up so that I kind of can't move. I turn off all the lights and just wait for it to pass.

NEIGHMOND: That can take hours. Scientists believe the pain is generated from deep inside the brain and somehow related to the wave of excited brain cells. What triggers a migraine is nearly as complicated as the migraine itself. There are environmental changes like sounds, light, smells and movement. There are genes. Migraines are hereditary. But there is a major trigger and this is why women have so many more migraines than men. Neurologist Jan Brandes says it's all about fluctuating hormones.

DR. JAN BRANDES: And it's that hormonal link that we feel accounts for the increase from adolescence through - essentially through menopause for the increased numbers of women with migraine over men.

NEIGHMOND: The likely culprit is estrogen, but scientists think a number of other hormones may be involved. It's the uncertainty about exactly what, why and how that makes treatment so difficult. There are medications to reduce the pain and length of a migraine. Others cut down on the frequency of attacks. But there is no cure. And as many as half of all patients say treatment isn't effective.

And nearly everyone says they'd happily try something new if it became available. And that's exactly what Dr. Charles is trying to do here at UCLA's headache lab, which bulges with microscopes, cameras, lasers, computers and, here and there, a mouse.

CHARLES: The mouse has a haircut and you can actually see changes in brain activity, you know, through the intact skull of a mouse that is asleep under anesthesia. It's resting comfortably.

NEIGHMOND: Charles is tracking how the mouse brain reacts to a caffeine-like substance. Caffeine can trigger migraines in humans. Finding effective treatment to reduce the number of attacks is critically important, says neurologist Jan Brandes, because migraines beget migraines.

BRANDES: We've begun to see that frequency of attack is linked to permanent changes in brain. And I think that changes the playing field because that means we really need to think carefully about controlling frequency of attack and we need to try to do it earlier rather than later.

NEIGHMOND: Especially, says Brandes, because damage to the brain caused by chronic migraines can increase the risk of stroke.